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2016 ; 7
(ä): 380
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English Wikipedia
A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in
Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide
Multi-Center Retrospective Observational Study
#MMPMID27822185
Vitale A
; Insalaco A
; Sfriso P
; Lopalco G
; Emmi G
; Cattalini M
; Manna R
; Cimaz R
; Priori R
; Talarico R
; Gentileschi S
; de Marchi G
; Frassi M
; Gallizzi R
; Soriano A
; Alessio M
; Cammelli D
; Maggio MC
; Marcolongo R
; La Torre F
; Fabiani C
; Colafrancesco S
; Ricci F
; Galozzi P
; Viapiana O
; Verrecchia E
; Pardeo M
; Cerrito L
; Cavallaro E
; Olivieri AN
; Paolazzi G
; Vitiello G
; Maier A
; Silvestri E
; Stagnaro C
; Valesini G
; Mosca M
; de Vita S
; Tincani A
; Lapadula G
; Frediani B
; De Benedetti F
; Iannone F
; Punzi L
; Salvarani C
; Galeazzi M
; Rigante D
; Cantarini L
Front Pharmacol
2016[]; 7
(ä): 380
PMID27822185
show ga
Background: Interleukin (IL)-1 inhibitors have been suggested as possible
therapeutic options in a large number of old and new clinical entities
characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide
snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab
(CAN) for different conditions both in children and adults. Methods: We
retrospectively collected demographic, clinical, and therapeutic data from both
adult and pediatric patients treated with IL-1 inhibitors from January 2008 to
July 2016. Results: Five hundred and twenty-six treatment courses given to 475
patients (195 males, 280 females; 111 children and 364 adults) were evaluated.
ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two
(32.1%) patients had been treated with both agents. IL-1 inhibitors were employed
in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more
frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic
approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors
were associated with corticosteroids in 285 (54.18%) courses and disease
modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from
30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among
children; regarding CAN, the most frequently used posologies were 150mg every 8
weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was
higher among patients treated with ANA at a dosage of 100 mg/day than those
treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an
adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after
the age of 65 compared to both children and patients aged between 16 and 65 (p =
0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used
off-label, especially ANA, during adulthood. The high frequency of good clinical
responses suggests that IL-1 inhibitors are used with awareness of pathogenetic
mechanisms; adult healthcare physicians generally employ standard dosages, while
pediatricians are more prone in using a weight-based posology. Dose adjustments
and switching between different agents showed to be effective treatment
strategies. Our data confirm the good safety profile of IL-1 inhibitors.